The Experts below are selected from a list of 40071 Experts worldwide ranked by ideXlab platform
Xiaoli Liu - One of the best experts on this subject based on the ideXlab platform.
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a high throughput Drug Screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer
Investigational New Drugs, 2019Co-Authors: Xiaoli Liu, Wei Wang, Yanping Yin, Hang XiangAbstract:Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput Drug Screen strategy to identify new Drugs that can enhance the sensitivity of chemo-Drug cisplatin in SCLC. This Screen identified auranofin, a US Food and Drug Administration (FDA)-approved Drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.
Hang Xiang - One of the best experts on this subject based on the ideXlab platform.
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a high throughput Drug Screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer
Investigational New Drugs, 2019Co-Authors: Xiaoli Liu, Wei Wang, Yanping Yin, Hang XiangAbstract:Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput Drug Screen strategy to identify new Drugs that can enhance the sensitivity of chemo-Drug cisplatin in SCLC. This Screen identified auranofin, a US Food and Drug Administration (FDA)-approved Drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.
Yanping Yin - One of the best experts on this subject based on the ideXlab platform.
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a high throughput Drug Screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer
Investigational New Drugs, 2019Co-Authors: Xiaoli Liu, Wei Wang, Yanping Yin, Hang XiangAbstract:Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput Drug Screen strategy to identify new Drugs that can enhance the sensitivity of chemo-Drug cisplatin in SCLC. This Screen identified auranofin, a US Food and Drug Administration (FDA)-approved Drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.
Frank Mccormick - One of the best experts on this subject based on the ideXlab platform.
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abstract 388 pathway directed high throughput Drug Screen identifies pi3k inhibitors that synergistically potentiate anti tumor activity of hdac inhibitors in mycosis fungoides and sezary syndrome
Cancer Research, 2016Co-Authors: Chenyen Yang, Razan Faraj, Taha Rakhshandaroo, Shervin Afghani, Laura B Pincus, Sourav Bandyopadhyay, Frank MccormickAbstract:Introduction and Purposes: Mycosis fungoides and Sezary syndrome (MF/SS) represent a group of heterogeneous diseases. Recent studies demonstrated dysregulation of several signaling pathways in MF/SS, including PI3K/AKT, JAK/STAT, RAS and NFκB pathways. We performed a high throughput Drug Screen to determine the potential of novel agents targeting these pathways for the treatment of MF/SS. Experimental Procedures: We compiled a library of 94 compounds targeting pathways known to be relevant in cancer biology. These included kinases involved in growth factor receptor signaling, HDACs, proteasome, DNA repair and regulators of apoptosis. The compounds were Screened for anti-proliferative activity against four MF/SS cell lines in high throughput proliferation assays. Selected hits were further studied in xenograft models of MF/SS and in primary T cell lymphomas. Promising candidates from different classes were also tested in combination therapy assays using a matrix block method across dose gradients of each compound designed to detect synergistic activities. Results: From the high throughput Screen, we identified 14 compounds with anti-proliferative activity in MF/SS, including multiple inhibitors of the PI3K pathway. PI3K inhibitors emerged as preliminary hits in this Screen and secondary validation assays confirmed the class effect of PI3K inhibitors. From this class, the PI3K inhibitor BKM120 was selected for in vivo studies. In a xenograft model of MF, BKM120 exhibited striking anti-tumor activity measured by a marked suppression of tumor growth and prolonged survival of tumor-bearing mice compared with vehicle control. In a search for even more effective combination therapies, we identified that BKM120 and the HDAC inhibitor class of compounds exhibit synergistic anti-proliferative effects in MF/SS tumor cells. Each of three HDAC inhibitors including LBH, Romidepsin and Vorinostat showed synergistic activity with BKM120, most evident at the GI50 concentrations of each Drug, and apparent in both growth inhibition and apoptotic assays. Conclusion: BKM120 is highly active in preclinical models of MF/SS. Furthermore, it synergistically potentiates the effect of HDAC inhibitors against MF/SS tumor cells. These are highly promising approaches for the treatment of MF/SS and warrant clinical investigation. Citation Format: Chen-Yen Yang, Razan Faraj, Taha Rakhshandaroo, Shervin Afghani, Laura Pincus, Sourav Bandyopadhyay, Frank McCormick, Weiyun Ai. Pathway-directed high throughput Drug Screen identifies PI3K inhibitors that synergistically potentiate anti-tumor activity of HDAC inhibitors in mycosis fungoides and Sezary syndrome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 388.
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pathway directed high throughput Drug Screen identifies pi3k inhibitors that synergistically potentiate anti tumor activity of hdac inhibitors in mycosis fungoides and sezary syndrome
Blood, 2015Co-Authors: Chenyen Yang, Razan Faraj, Shervin Afghani, Laura B Pincus, Sourav Bandyopadhyay, Taha Rakhshandhroo, Frank MccormickAbstract:Introduction and Objectives: Mycosis fungoides and Sezary syndrome (MF/SS) represent a group of heterogeneous diseases. Recent studies demonstrated dysregulation of several signaling pathways in MF/SS, including PI3K/AKT, JAK/STAT, RAS and NFkB pathways. We performed a high throughput Drug Screen to determine the potential of novel agents targeting these pathways for the treatment of MF/SS. Materials and Methods: We compiled a libraryof 94 compounds targeting pathways known to be relevant in cancer biology. These included kinases involved in growth factor receptor signaling, HDACs, proteasome, DNA repair and regulators of apoptosis. The compounds were Screened for anti-proliferative activity against four MF/SS cell lines in high throughput proliferation assays. Selected hits were further studied in xenograft models of MF/SS and in primary T cell lymphomas. Promising candidates from different classes were also tested in combination therapy assays using a matrix block method across dose gradients of each compound designed to detect synergistic activities. Results: From the high throughput Screen, we identified 14 compounds with anti-proliferative activity in MF/SS, including multiple inhibitors of the PI3K pathway. PI3K inhibitors emerged as preliminary hits in this Screen and secondary validation assays confirmed the class effect of PI3K inhibitors. From this class, the PI3K inhibitor BKM120 was selected for in vivo studies. In a xenograft model of MF, BKM120 exhibited striking anti-tumor activity measured by a marked suppression of tumor growth and prolonged survival of tumor-bearing mice compared with vehicle control. In a search for even more effective combination therapies, we identified that BKM120 and the HDAC inhibitor class of compounds exhibit synergistic anti-proliferative effects in MF/SS tumor cells. Each of three HDAC inhibitors including LBH, Romidepsin and Vorinosat showed synergistic activity with BKM120, most evident at the GI50 concentrations of each Drug, and apparent in both growth inhibition and apoptotic assays. Conclusion: BKM120 is highly active in preclinical models of MF/SS. Furthermore, it synergistically potentiates the effect of HDAC inhibitors against MF/SS tumor cells. These are highly promising approaches for the treatment of MF/SS and warrant clinical investigation. Disclosures No relevant conflicts of interest to declare.
Wei Wang - One of the best experts on this subject based on the ideXlab platform.
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a high throughput Drug Screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer
Investigational New Drugs, 2019Co-Authors: Xiaoli Liu, Wei Wang, Yanping Yin, Hang XiangAbstract:Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput Drug Screen strategy to identify new Drugs that can enhance the sensitivity of chemo-Drug cisplatin in SCLC. This Screen identified auranofin, a US Food and Drug Administration (FDA)-approved Drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.
